A pediatric randomized, controlled trial of German cockroach subcutaneous immunotherapy.

BACKGROUND: Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children. OBJECTIVES: We sought to determine whether nasal allergen challenge (NAC) responses to cockroach allergen would improve following 1 year of SCIT. METHODS: Urban children with asthma, who were cockroach-sensitized and reactive on NAC, participated in a year-long randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean Total Nasal Symptom Score (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test wheal size, serum allergen-specific antibody production, and T-cell responses to cockroach allergen were assessed. RESULTS: Changes in mean NAC TNSS did not differ between SCIT-assigned (n = 28) versus placebo-assigned (n = 29) participants (P = .63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum-specific IgE decreased to a similar extent in both groups, while decreased cockroach skin prick test wheal size was greater among SCIT participants (P = .04). A 200-fold increase in cockroach serum-specific IgG4 was observed among subjects receiving SCIT (P < .001) but was unchanged in the placebo group. T-cell IL-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (P = .002), while no effect was observed for IL-10 or IFN-γ. CONCLUSIONS: A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum-specific IgG4 serum production and down-modulation of allergen-stimulated T-cell responses.

A holistic analysis of collective behaviour and team performance in Australian Football via structural equation modelling.

Despite awareness of the importance of quantifying technical, tactical, and physical characteristics of match play, few studies have examined the structural relationship of these aspects in professional sport. Accordingly, this study concurrently examined these components in relation to quarter outcome (n = 272) in Australian Football. The study followed a retrospective longitudinal case study design where one teams' cooperative passing network, skill counts, physical loads, and spatiotemporal behaviours during official Australian Football League games were collected from a period spanning four seasons (2016-2019). A principal components analysis (PCA) and structural equation modelling were used to explore the structural relationships between components and examine the influence on quarter outcome as determined by the point differential (quarter margin). Scoring opportunity and ball movement had direct associations with quarter margin, while unpredictability, uncontested behaviour and physical behaviour did not. Negative associations between uncontested behaviour and scoring opportunity suggest that elevated high-pressure success and a lack of synchrony may positively influence scoring opportunity, a determinant of quarter margin. Further, negative associations between physical behaviour and ball movement suggest that with less physical work, a team's collective ability to transfer possession between teammates is facilitated, offering an interesting dichotomy between skill and physical demands of Australian Football. While hundreds of different metrics are available, the present study was the first to concurrently examine the influence of a variety of match play components on performance outcomes in Australian Football. These results may provide direction for coaches and practitioners when contemplating practice design, tactical strategies, or the development of behaviour through specific training exercises. Game plans and training drills that focus on optimising attacking and low-pressure ball movement coupled with high levels of mutual interaction between teammates may be beneficial for performance.

HEPA filtration intervention in classrooms may improve some students' asthma.

OBJECTIVE: The School Inner-City Asthma Intervention Study 2 (SICAS 2) tested interventions to reduce exposures in classrooms of students with asthma. The objective of this post-hoc analysis was limited to evaluating the effect of high-efficiency particulate (HEPA) filtration interventions on mold levels as quantified using the Environmental Relative Moldiness Index (ERMI) and the possible improvement in the students' asthma, as quantified by spirometry testing. METHODS: Pre-intervention dust samples were collected at the beginning of the school year from classrooms and corresponding homes of students with asthma (n = 150). Follow-up dust samples were collected in the classrooms at the end of the HEPA or Sham intervention. For each dust sample, ERMI values and the Group 1 and Group 2 mold levels (components of the ERMI metric) were quantified. In addition, each student's lung function was evaluated by spirometry testing, specifically the percentage predicted forced expiratory volume at 1 sec (FEV1%), before and at the end of the intervention. RESULTS: For those students with a higher Group 1 mold level in their pre-intervention classroom than home (n = 94), the FEV1% results for those students was significantly (p < 0.05) inversely correlated with the Group 1 level in their classrooms. After the HEPA intervention, the average Group 1 and ERMI values were significantly lowered, and the average FEV1% test results significantly increased by an average of 4.22% for students in HEPA compared to Sham classrooms. CONCLUSIONS: HEPA intervention in classrooms reduced Group 1 and ERMI values, which corresponded to improvements in the students' FEV1% test results.

The Coronavirus Disease 2019 Pandemic and Mental Health-Related School-Nurse Visits in United States Schools.

OBJECTIVE: No studies have examined school-nurse visits related to mental health (MH) during the coronavirus disease 2019 (COVID-19) pandemic. We examined changes in the rate of MH-related school-nurse visits before and during the COVID-19 pandemic. METHODS: We analyzed school-nurse visit data (n = 3,445,240) for subjects Grade K-12 in US public schools using electronic health record software (SchoolCare, Ramsey, NJ). Data between January 1 and December 31 in 2019 (pre-COVID-19 pandemic) versus January 1 to December 31 in 2020 (during COVID-19 pandemic) were compared. For each year, total visits to a school-nurse were calculated for general MH, anxiety, and self-harm. The exposure was number of school-nurse visits in each time period (2019 vs 2020). The main outcome was change in the rate of general MH, anxiety, and self-harm visits in 2019 versus 2020. RESULTS: There were 2,302,239 total school-nurse visits in 2019 versus 1,143,001 in 2020. During the COVID-19 pandemic, the rate of visits for general MH increased by 30% (4.7-6.1 per 10,000 visits, 95% confidence interval [CI] {18%, 43%}; P < .001), and visits for anxiety increased by 25% (24.8-31 per 10,000 visits, 95% CI [20%,30%]; P < .001). There was no significant difference in self-harm visits across all ages during the COVID-19 pandemic. CONCLUSIONS: Our study found a significant increase in the rate of school-nurse visits for MH and anxiety during the COVID-19 pandemic, suggesting the pediatric population is at-risk for increased negative MH-effects associated with the pandemic and highlights a critical role of school-nurses in identifying youth with potential MH-needs.

Phases of Match-Play in Professional Australian Football: Positional Demands and Match-Related Fatigue.

This study examined the influence of player position and match quarter on activity profiles during the phases of play in Australian Football. Global positioning satellite data was collected for one season from an Australian Football League team for nomadic, key position and ruck players (age: 24.8 ± 4.2 years, body mass: 88.3 ± 8.7 kg, height: 1.88 ± 0.8 m). Separate linear mixed models and effect sizes were used to analyse differences between positions and game quarter within each phase of play for values of distance, speed and metabolic power indices. There were clear differences between positions for low-speed running, high-speed running, total distance and average speed. Nomadic players generally recorded the highest match running outputs, followed by key position players and ruckmen. Within each position, offence and defence involved the highest intensities, followed by contested play and then stoppage periods. Across the four quarters, there were small to large reductions in average speed, high-speed running, high power and energy expenditure during offence, defence and contested play, but not during stoppages. Accordingly, conditioning staff should consider the intermittent intensities of the phases of match-play for each position to optimally prepare players for competition. Reductions in match intensities were evident during active periods of play providing implications for real-time monitoring to optimise the timing of rotations.

Factors associated with cooperative network connectedness in a professional Australian football small-sided game.

OBJECTIVES: Connectedness is a cooperative network measure that describes how well players in the team bi-directionally connect and how easily reachable they are to other players. It has been associated with an increased probability of winning competitive matches in professional Australian Football (AF), although applications towards training have not been reported. Therefore, this study investigated associations between constraints manipulated by professional AF coaches and the connectedness of cooperative passing networks during a small-sided game (SSG). DESIGN: Data were collected describing the task constraints manipulated by professional coaches across one SSG performed on multiple occasions. The SSG focused on transitioning between defence and attack and was performed fifteen times across a whole season, resulting in 36 observations of team connectedness. METHOD: A linear mixed-effects model was constructed to examine the collective influence of constraints manipulations made by professional coaches (e.g. field size) and team skill characteristics (e.g. kick efficiency) on connectedness scores. RESULTS: The number of team shots on goal and the time on task both positively contributed to connectedness scores, explaining 65% of its variance. CONCLUSION: The findings show that the number of shots on goal and the time on task may be used to elicit higher or lower connectedness scores in AF SSGs. Skill acquisition specialists, in conjunction with coaching staff, can use these metrics to aid practice design in professional AF or indeed other invasion-style team sports.

Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: Black and Hispanic children living in urban environments in the USA have an excess burden of morbidity and mortality from asthma. Therapies directed at the eosinophilic phenotype reduce asthma exacerbations in adults, but few data are available in children and diverse populations. Furthermore, the molecular mechanisms that underlie exacerbations either being prevented by, or persisting despite, immune-based therapies are not well understood. We aimed to determine whether mepolizumab, added to guidelines-based care, reduced the number of asthma exacerbations during a 52-week period compared with guidelines-based care alone. METHODS: This is a randomised, double-blind, placebo-controlled, parallel-group trial done at nine urban medical centres in the USA. Children and adolescents aged 6-17 years, who lived in socioeconomically disadvantaged neighbourhoods and had exacerbation-prone asthma (defined as ≥two exacerbations in the previous year) and blood eosinophils of at least 150 cells per µL were randomly assigned 1:1 to mepolizumab (6-11 years: 40 mg; 12-17 years: 100 mg) or placebo injections once every 4 weeks, plus guideline-based care, for 52 weeks. Randomisation was done using a validated automated system. Participants, investigators, and the research staff who collected outcome measures remained masked to group assignments. The primary outcome was the number of asthma exacerbations that were treated with systemic corticosteroids during 52 weeks in the intention-to-treat population. The mechanisms of treatment response were assessed by study investigators using nasal transcriptomic modular analysis. Safety was assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03292588. FINDINGS: Between Nov 1, 2017, and Mar 12, 2020, we recruited 585 children and adolescents. We screened 390 individuals, of whom 335 met the inclusion criteria and were enrolled. 290 met the randomisation criteria, were randomly assigned to mepolizumab (n=146) or placebo (n=144), and were included in the intention-to-treat analysis. 248 completed the study. The mean number of asthma exacerbations within the 52-week study period was 0·96 (95% CI 0·78-1·17) with mepolizumab and 1·30 (1·08-1·57) with placebo (rate ratio 0·73; 0·56-0·96; p=0·027). Treatment-emergent adverse events occurred in 42 (29%) of 146 participants in the mepolizumab group versus 16 (11%) of 144 participants in the placebo group. No deaths were attributed to mepolizumab. INTERPRETATION: Phenotype-directed therapy with mepolizumab in urban children with exacerbation-prone eosinophilic asthma reduced the number of exacerbations. FUNDING: US National Institute of Allergy and Infectious Diseases and GlaxoSmithKline.

Atopic Dermatitis Mediates the Association Between an IL4RA Variant and Food Allergy in School-Aged Children.

BACKGROUND: Atopic dermatitis (AD) and food allergy (FA) may share genetic risk factors. It is unknown whether genetic factors directly cause FA or are mediated through AD, as the dual-allergen hypothesis suggests. OBJECTIVE: To test the hypothesis that AD mediates the relationship between an IL-4 receptor alpha chain gene (IL4RA) variant, the human IL-4 receptor alpha chain protein-R576 polymorphism, and FA. METHODS: A total of 433 children with asthma enrolled in the School Inner-City Asthma Study underwent genotyping for the IL4RA576 allele. Surveys were administered to determine FA, AD, and associated allergic responses. Mediation analysis was performed adjusting for race and ethnicity, age, sex, and household income. Multivariate models were used to determine the association between genotype and FA severity. RESULTS: AD was reported in 193 (45%) and FA in 80 children (19%). Each risk allele increased odds of AD 1.39-fold ([1.03-1.87], P = .03), and AD increased odds of FA 3.67-fold ([2.05- 6.57], P < .01). There was an indirect effect of genotype, mediated by AD, predicting FA; each risk allele increased the odds of FA by 1.13 (odds ratio [95% CI], Q/R = 1.13 [1.02-1.24], R/R = 1.28 [1.04-1.51]; P < .01). Each risk allele increased the odds of severe FA symptoms 2.68-fold ([1.26-5.71], P = .01). CONCLUSIONS: In a cohort of children with asthma, AD is part of the causal pathway between an IL4RA variant and FA. This variant is associated with increased risk of severe FA reactions. Addressing AD in children with an IL4RA polymorphism may modulate the risk of FA.

Tactical analysis of individual and team behaviour in professional Australian Football.

INTRODUCTION: This study sought to reduce the dimensionality of commonly reported spatiotemporal characteristics obtained from Australian Football games to facilitate their practical use and interpretability. METHODS: A retrospective longitudinal design was utilised with team and individual spatiotemporal variables, measured via global navigation satellite system devices, collected during official Australian Football League matched over three seasons. Two separate principal component analyses were conducted at the team and individual level to reduce correlated spatiotemporal characteristics into a smaller set of uncorrelated components. RESULTS: At the team level, eighteen variables were reduced to five components pertaining to dispersive coordination, lateral predictability and spacing, multidirectional synchrony, longitudinal predictability and longitudinal behaviour whilst maintaining 69% of variance in the original dataset. At the individual level, fifteen variables were reduced to four components pertaining to multidirectional and spacing synchrony, unpredictability, player movement and player positioning whilst maintaining 64% of variance. CONCLUSION: This study is the first to provide a simplified, novel method for analysing spatiotemporal behaviour in an Australian Football context with both the team- and individual- derived metrics revealing useful information for coaches and practitioners. Components may provide insight into behaviours that emerge and persist throughout a game and allow coaches to distinguish between different playing/behavioural styles.

Collective behaviour in high and low-level youth soccer teams.

BACKGROUND: An expert/non-expert paradigm often helps understand the underpinnings of sports expertise; however, this method is scarcely extended to the complexities of collective behaviour in youth soccer. AIM: Therefore, the objectives of the current study are to investigate differences in the collective behaviour of youth soccer teams by expertise level. METHODOLOGY: Soccer players aged 15 to 20 years from high (n = 35) and low (n = 40) playing levels competed in two age-matched 5v5 small-sided games. For each game, teams' skill involvement (shot, pass, dribble, touch), passing networks (closeness, density, betweenness), and spatiotemporal characteristics (stretch index, effective area, length (L) & width (W), LpW ratio, synchrony) were measured using video footage and GPS coordinates. RESULTS: High level teams had more attempted (p = .009), and completed skills (p = .003), particularly for the number of passes (p = .001) and shots (p = .012-.045). However, there were no significant between-group differences for either the passing networks or spatiotemporal characteristics. CONCLUSION: The findings from the current research suggest that the high-level teams can quickly and effectively move the ball within existing team structures and may better optimise their afforded space to execute desired skills when compared to the low-level teams.

Physical Determinants of Golf Swing Performance: A Review.

ABSTRACT: Sheehan, WB, Bower, RG, and Watsford, ML. Physical determinants of golf swing performance: A review. J Strength Cond Res 36(1): 289-297, 2022-Traditionally, golf practice has primarily focused on the mental, technical, and skill aspects as the primary means to improve performance. Only recently has a greater emphasis been placed on the physical components with balance, muscular strength, power, and specific muscle-tendon properties demonstrating positive associations with club head speed and carry distance. Accordingly, this review will explore the influence of these physical components on measures of golf swing performance. Superior balance may allow players to effectively deal with the need to shift weight during the swing as well as different stance positions, whereas superior lower-body muscular strength, power, and stiffness may allow more mechanical work to be performed on the club during the swing per unit of time, consequently increasing club head speed. Alternatively, flexibility may also contribute to enhanced force production with a greater range of motion, particularly when generating the "X-factor," allowing for a longer backswing and more time to produce higher angular velocities and forces. Furthermore, training intervention studies focusing on the aforementioned components have demonstrated enhancements in swing performance. Targeting multiple muscle groups, including those implicated via electromyography activation, and utilizing multiple modalities have proven effective at increasing club head speed. However, such multifaceted programs have made it difficult to determine the mechanisms that specifically contribute to performance gains. Despite these limitations, strength, power, and musculotendinous stiffness, particularly in the lower body, seem to be stronger determinants of club head speed and carry distance than flexibility. Furthermore, acute improvements can be induced using resistance-orientated warm-ups.

Match simulation practice may not represent competitive match play in professional Australian football.

Match simulation in team sport should sample representative constraints and behaviours to those observed in competitive matches to enhance near skill transfer. This study compared task constraints (field length, field width, length per width ratio, space per player), time-standardised skill metrics (goals, shots on goal, handballs, kicks, marks, turnovers, tackles, handball proficiency, kick proficiency) and cooperative passing metrics (connectedness, indegree variability and outdegree variability) between match simulation practice and competitive Australian Football League (AFL) games for one professional team. MANOVAs identified activity-related differences for task constraints, skill metrics and cooperative passing networks. During match simulation, goals were scored more frequently, but with less passing actions per minute. Receiving and distributing passing networks were more centralised (reliance on fewer key individuals), with less turnovers and tackles per minute compared to AFL matches. If match simulation is designed to reflect competition, then player and team skill preparation may be compromised. Furthermore, the competing demands in high-performance sport may restrict the degree of representativeness that can be achieved during practice. These findings provide valuable insight and may assist practitioners and/or coaches to understand the value of match simulation practice and to maximise near skill transfer from match simulation to competition.

Effect of School Integrated Pest Management or Classroom Air Filter Purifiers on Asthma Symptoms in Students With Active Asthma: A Randomized Clinical Trial.

Importance: School and classroom allergens and particles are associated with asthma morbidity, but the benefit of environmental remediation is not known. Objective: To determine whether use of a school-wide integrated pest management (IPM) program or high-efficiency particulate air (HEPA) filter purifiers in the classrooms improve asthma symptoms in students with active asthma. Design, Setting, and Participants: Factorial randomized clinical trial of a school-wide IPM program and HEPA filter purifiers in the classrooms was conducted from 2015 to 2020 (School Inner-City Asthma Intervention Study). There were 236 students with active asthma attending 41 participating urban elementary schools located in the Northeastern US who were randomized to IPM by school and HEPA filter purifiers by classroom. The date of final follow-up was June 20, 2020. Interventions: The school-wide IPM program consisted of application of rodenticide, sealing entry points, trap placement, targeted cleaning, and brief educational handouts for school staff. Infestation was assessed every 3 months, with additional treatments as needed. Control schools received no IPM, cleaning, or education. Classroom portable HEPA filter purifiers were deployed and the filters were changed every 3 months. Control classrooms received sham HEPA filters that looked and sounded like active HEPA filter purifiers. Randomization was done independently (split-plot design), with matching by the number of enrolled students to ensure a nearly exact 1:1 student ratio for each intervention with 118 students randomized to each group. Participants, investigators, and those assessing outcomes were blinded to the interventions. Main Outcomes and Measures: The primary outcome was the number of symptom-days with asthma during a 2-week period. Symptom-days were assessed every 2 months during the 10 months after randomization. Results: Among the 236 students who were randomized (mean age, 8.1 [SD, 2.0] years; 113 [48%] female), all completed the trial. At baseline, the 2-week mean was 2.2 (SD, 3.9) symptom-days with asthma and 98% of the classrooms had detectable levels of mouse allergen. The results were pooled because there was no statistically significant difference between the 2 interventions (P = .18 for interaction). During a 2-week period, the mean was 1.5 symptom-days with asthma after use of the school-wide IPM program vs 1.9 symptom-days after no IPM across the school year (incidence rate ratio, 0.71 [95% CI, 0.38-1.33]), which was not statistically significantly different. During a 2-week period, the mean was 1.6 symptom-days with asthma after use of HEPA filter purifiers in the classrooms vs 1.8 symptom-days after use of sham HEPA filter purifiers across the school year (incidence rate ratio, 1.47 [95% CI, 0.79-2.75]), which was not statistically significantly different. There were no intervention-related adverse events. Conclusions and Relevance: Among children with active asthma, use of a school-wide IPM program or classroom HEPA filter purifiers did not significantly reduce symptom-days with asthma. However, interpretation of the study findings may need to consider allergen levels, particle exposures, and asthma symptoms at baseline. Trial Registration: ClinicalTrials.gov Identifier: NCT02291302.

Detection of Food Allergens in School and Home Environments of Elementary Students.

BACKGROUND: Little is known about environmental food allergen exposure on school surfaces. OBJECTIVE: To compare the distribution of major food allergens in floor dust and table wipe samples from elementary schools and dust samples from students' homes. METHODS: In this substudy of the School Inner-City Asthma Study-II, 103 table wipe samples and 98 floor dust samples from cafeterias and classrooms in 18 elementary schools were analyzed for milk, peanut, cashew, hazelnut, and egg using a multiplex array. Home kitchen floor and bed dust samples from 90 students were also analyzed. RESULTS: Food allergens were detectable in schools, but at significantly lower levels than in homes (P < .001). In schools, milk and peanut were detected in all table wipe samples; milk and egg were detected in all floor dust samples. Cafeteria table wipe samples contained significantly higher levels of milk, peanut, hazelnut, and egg, compared with classrooms. Cafeteria floor dust samples contained higher levels milk than classrooms. Peanut-restrictive policies did not consistently reduce environmental peanut exposure in schools. Peanut allergen was lower in dust from homes of students with peanut allergy (n = 5) compared with those without peanut allergy (n = 85) (P < .001). Reassuringly, peanut allergen in the schools of peanut-allergic students was not significantly different than in their homes. CONCLUSION: Food allergens were readily detectable on tables and floors in elementary schools, but at levels lower than in students' homes. For peanut-allergic students, the levels of detectable peanut in their schools were not higher than their homes. The low levels of detectable food allergens in school environments are unlikely to result in severe allergic reactions.

An assessment of physical and spatiotemporal behaviour during different phases of match play in professional Australian football.

Despite advancements in the scale of data available for quantifying the physical and spatiotemporal characteristics of match play, there is an absence of research combining these aspects in professional sport. This study sought to differentiate between phases of play in professional Australian football using novel physical and spatiotemporal metrics. Data was obtained from Australian Football League games to provide new insight into the specific characteristics of each phase of play. A retrospective cross-sectional design was utilised with team's physical and spatiotemporal variables, measured via global navigation satellite system devices. A multinomial logistic regression was conducted to determine which physical and spatiotemporal measures were associated with each phase of play (contested play, defence, offence, set shot, goal reset, umpire stoppage). The addition of the predictors to a model that contained only the intercept significantly improved the fit between the model and data, with the logistic model correctly predicting the phase of play for 63.7% of the cases. This was the first study to concurrently examine differences in physical and spatiotemporal characteristics with respect to phase of play in an Australian football context. Differences in duration, physical and spatiotemporal properties were observed, providing new insight for coaches and subsequently providing direction for conditioning and practice design.

Adherence rates during a randomized controlled trial evaluating the use of blinded acetaminophen and ibuprofen in children with asthma.

BACKGROUND/AIMS: When conducting clinical trials comparing over-the-counter (OTC) medications, the wide availability of these treatments are a potential challenge to maintaining study integrity. We seek to describe adherence to a study protocol involving widely available OTC medications. METHODS: To prospectively evaluate associations between acetaminophen use and asthma in 300 children aged 1-5 years, we conducted a double blind, randomized, controlled trial where parents administered blinded forms of either acetaminophen or ibuprofen as needed to their children over a 48 week period. Written and verbal instructions encouraged the exclusive use of the blinded study medication and discouraged OTC use. Adherence was determined by evaluating the frequency of use of per-protocol blinded study medication compared to off-protocol use of OTC medications. RESULTS: 4195 doses of acetaminophen or ibuprofen were received by children during the study which included 3664 doses (87.3%) of blinded study medication adhering to the protocol and 531 doses (12.7%) of OTC products deviating from the protocol with better adherence among those randomized to ibuprofen as compared to acetaminophen (89.5% vs. 85.5% of doses, p < 0.01). Individually, 227 participants (75.7%) remained fully adherent by not receiving any OTC medications. Pre-study preference for either acetaminophen or ibuprofen by the participants' families was not associated with differential rates of adherence to the blinded medication. CONCLUSION: This parallel study demonstrated greater than 85% of acetaminophen or ibuprofen doses were blinded study medications adhering to the protocol while less than 15% were OTC deviations from the protocol. This successfully implemented study design provides a template to comparatively evaluate these and other OTC medications.